Analogues of the growth hormone-release inhibiting factor (GIF), H- Ala-Gly-Cys-Lys-Asn- Phe-Phe-Trp-Lys-Thr-Phe- Thr-Ser-Cys-OH, also known as somatostatin, will be synthesized by the Merrifield solid phase technique and examined in vivo and in vitro for their effects on secretion of immunoreactive growth hormone from the rat adenohypophysis and possibly on the secretion of glucagon and insulin. On the basis of this work, conclusions could be drawn as to the relationship between structure of this tetradecapeptid and biological activity. This in turn would make possible the synthesis of compounds that might have greater clinical usefulness than the natural GIF material in the treatment of acromegaly and angiopathies associated with diabetes mellitus and for selective inhibition of glucagon secretion in juvenile diabetes. In particular, the development of long-acting analogues with much greater biological half-life than somatostatin is considered to be of great importance. Suitable analogs would be assayed also for competitive inhibition of somatostatin on the assumption that such materials could function as growth hormone-releasing factors of potential practical value.